Our research now encompasses 12 projects in syntheses of alkaloids with established medicinal use. Of these, 8 syntheses are directed at compounds with anticancer activity. In additional projects we are pursuing oncolytic activity through syntheses of a series of quinolinooxazines and are examining chemical constituents of food ferns for their implication as carcinogens. The alkaloid syntheses focus on practical total syntheses of the clinically useful anticancer drug vinblastine (VLB) with multiple synthetic routes to its vindoline and carbomethoxyvelbanamine or catharanthine precursor moieties. We are also studying coupling reactions of these indole and dihydroindole alkaloids to produce VLB. These syntheses are designed to provide skeletal structure modifications which will allow an examination of a hypothesis for VLB binding to tubulin, i.e., reveal the mechanism of action of VLB, and also furnish a VLB modification free of neurotoxicity. Our syntheses are based either on a biomimetic approach through secodine intermediates or on oxindoles. These principles are extended to strychnos and aspidospermatine alkaloids. A practical synthesis of cephalotaxine, the parent alcohol of the oncolytic harringtonine esters, is adaptable to structure-activity studies based on changes in the alkaloid skeleton.